Parkinson’s disease is by far the most common neurodegenerative movement disorder; the clinical spectrum of Parkinson’s disease extends beyond dysfunctional motor control, with nonmotor symptoms being the initial symptoms of the disease, many years before the first typical motor symptoms appear. Idiopathic rapid eye movement sleep behavior disorder, a state of deep sleep characterized by loss of muscle tone during idiopathic rapid eye movement sleep, appears to have the highest predictive value for all nonmotor symptoms associated with an increased risk of Parkinson’s disease.Iranzo and colleagues report the results of long-term follow-up of 44 patients with sleep behavior disorder. Patients were followed for a mean of 6 years since diagnosis (12 years of follow-up after subjective recall of the first symptom of RBD), and 82% of patients were clinically determined to have transitioned to a 1/4 neurodegenerative syndrome, of which 36% had Parkinson’s disease and 32% had Lewy body dementia. Importantly, these clinical diagnoses were confirmed after three case autopsies, i.e., neuronal loss and Lewy body pathology were also documented in brainstem nuclei associated with idiopathic rapid eye movement tone deficit modulation. Clearly, the finding adds to the fundamental question of how to define Parkinson’s disease. The current diagnostic criteria for Parkinson’s disease have recently been discussed by a panel of experts around the issue of not only bringing the possibility of the disease having an early premotor phase through increasing evidence, but also linking it to a number of identified Parkinson’s disease genotypes through different pathologies. Biomarkers to identify Parkinson’s disease pathology are not available at this time, but efforts are being made to identify candidates. When referring to disease palliative therapies, there seems to be a great need for earlier diagnosis of Parkinson’s disease before it is based on defined diagnostic criteria. Unfortunately, this treatment remains an ambiguous target, and another negative disease palliation trial with a delayed-start design was published in 2013 that failed to detect differences in motor outcomes with earlier or later treatment with the dopamine agonist pramipexole, assessed with the Unified Parkinson’s Disease Rating Scale, and reduced dopamine transporter protein binding in the striatum was performed with I-FP-CIT SPECT assessment. Deep brain stimulation of the thalamic nucleus via implanted electrodes has become a first-line treatment for patients who do not achieve good motor control with pharmacological therapy. Several well-conducted randomized controlled trials have shown the effectiveness and superiority of deep brain stimulation over the best treatments for patients with persistent Parkinson’s disease with a mean disease duration of 12 years. Whether neurostimulation interventions improve quality of life with early motor symptoms over the course of the disease was recently evaluated in the EARLYSTIM trial. Researchers randomly assigned 251 patients (mean age 52 years, mean duration of disease 7.5 years) with recent episodes of levodopa-induced motor complications (no less than 3 years) to receive either a combination of deep brain stimulation of the nucleus accumbens plus best medical therapy or best medical therapy alone. After two years of follow-up, early deep brain stimulation was found to significantly improve the patients’ standard of living, motor impairment, activities of daily living, and levodopa-induced motor complications compared to best medical therapy. It has been claimed that deep brain stimulation should be considered immediately after the first appearance of motor complications. This concept seems premature for several reasons: because of the highly selected population enrolled in this trial, representing probably less than 5% of all patients in specialty center hospitals. The particularly high suicide rate in this trial may be an additional indication that patients differ from the general Parkinson’s disease population. In addition, this confounding effect of patient expectation is difficult to analyze in an unblinded study like EARLY-STIM. Long-term results from this cohort will help elucidate the benefits of deep brain stimulation on early motor complications in patients with Parkinson’s disease. For so-called atypical Parkinson’s conditions, such as multisystem atrophy, progressive supranuclear palsy or corticobasal degeneration, there is no effective treatment yet, and patients experience a brutally unrelenting progressive course with severe disability and eventual death within 10 years. There are very few studies on disease palliative treatment for these neurodegenerative conditions and the few studies that have been conducted (mainly in multisystem atrophy) have failed. In 2013, the Japanese Society and international investigators reported for the first time the potential cause of mutations in the COQ2 gene, which encodes an enzyme essential for the biosynthesis of coenzyme Q10, found in two families of multiple system atrophy. Mutations in the same gene with impaired function were associated with occasional multisystem atrophy in the Japanese subgroup in this study, including more than 800 patients. These results highlight impaired mitochondrial energy metabolism as an important pathogenic pathway in multisystem atrophy and a potential target for new therapies. Genetic testing can now identify asymptomatic individuals with inherited movement disorders such as Huntington’s disease or spinal cerebellar ataxia (SCA). the TRACK-HD study of 298 pre-displayed individuals and patients with early Huntington’s disease eventually found a variety of markers for the progression of Huntington’s disease independent of age and CAG length. SCA1, SCA2, SCA3, or SCA6, or the absence of positive genes, were measured in 264 offspring or siblings of patients for whom baseline data from this study have been reported and for whom outcome assessment at continued follow-up has been long awaited. The results of these observational cohort studies have important implications not only for the design of future clinical trials in Huntington’s disease and spinal cerebellar ataxia, but also have exemplary implications in the area of microbial markers for other more prevalent neurodegenerative disorders, such as incidental Alzheimer’s disease and Parkinson’s disease, for which there are no feasible highly predictive tests in the preclinical period.